SummaryThe suite of graphene’s unique properties and applications can be enormously enhanced by its functionalization. As non-covalently functionalized graphenes do not target all graphene’s properties and may suffer from limited stability, covalent functionalization represents a promising way for controlling graphene’s properties. To date, only a few well-defined graphene derivatives have been introduced. Among them, fluorographene (FG) stands out as a prominent member because of its easy synthesis and high stability. Being a perfluorinated hydrocarbon, FG was believed to be as unreactive as the two-dimensional counterpart perfluoropolyethylene (Teflon®). However, our recent experiments showed that FG is not chemically inert and can be used as a viable precursor for synthesizing graphene derivatives. This surprising behavior indicates that common textbook grade knowledge cannot blindly be applied to the chemistry of 2D materials. Further, there might be specific rules behind the chemistry of 2D materials, forming a new chemical discipline we tentatively call 2D chemistry. The main aim of the project is to explore, identify and apply the rules of 2D chemistry starting from FG. Using the knowledge gained of 2D chemistry, we will attempt to control the chemistry of various 2D materials aimed at preparing stable graphene derivatives with designed properties, e.g., 1-3 eV band gap, fluorescent properties, sustainable magnetic ordering and dispersability in polar media. The new graphene derivatives will be applied in sensing, imaging, magnetic delivery and catalysis and new emerging applications arising from the synergistic phenomena are expected. We envisage that new applications will be opened up that benefit from the 2D scaffold and tailored properties of the synthesized derivatives. The derivatives will be used for the synthesis of 3D hybrid materials by covalent linking of the 2D sheets joined with other organic and inorganic molecules, nanomaterials or biomacromolecules.

The suite of graphene’s unique properties and applications can be enormously enhanced by its functionalization. As non-covalently functionalized graphenes do not target all graphene’s properties and may suffer from limited stability, covalent functionalization represents a promising way for controlling graphene’s properties. To date, only a few well-defined graphene derivatives have been introduced. Among them, fluorographene (FG) stands out as a prominent member because of its easy synthesis and high stability. Being a perfluorinated hydrocarbon, FG was believed to be as unreactive as the two-dimensional counterpart perfluoropolyethylene (Teflon®). However, our recent experiments showed that FG is not chemically inert and can be used as a viable precursor for synthesizing graphene derivatives. This surprising behavior indicates that common textbook grade knowledge cannot blindly be applied to the chemistry of 2D materials. Further, there might be specific rules behind the chemistry of 2D materials, forming a new chemical discipline we tentatively call 2D chemistry. The main aim of the project is to explore, identify and apply the rules of 2D chemistry starting from FG. Using the knowledge gained of 2D chemistry, we will attempt to control the chemistry of various 2D materials aimed at preparing stable graphene derivatives with designed properties, e.g., 1-3 eV band gap, fluorescent properties, sustainable magnetic ordering and dispersability in polar media. The new graphene derivatives will be applied in sensing, imaging, magnetic delivery and catalysis and new emerging applications arising from the synergistic phenomena are expected. We envisage that new applications will be opened up that benefit from the 2D scaffold and tailored properties of the synthesized derivatives. The derivatives will be used for the synthesis of 3D hybrid materials by covalent linking of the 2D sheets joined with other organic and inorganic molecules, nanomaterials or biomacromolecules.

Max ERC Funding

1 831 103 €

Duration

Start date: 2016-06-01, End date: 2021-05-31

Project acronymAMSEL

ProjectAtomic Force Microscopy for Molecular Structure Elucidation

Researcher (PI)Leo Gross

Host Institution (HI)IBM RESEARCH GMBH

Call DetailsConsolidator Grant (CoG), PE4, ERC-2015-CoG

SummaryMolecular structure elucidation is of great importance in synthetic chemistry, pharmacy, life sciences, energy and environmental sciences, and technology applications. To date structure elucidation by atomic force microscopy (AFM) has been demonstrated for a few, small and mainly planar molecules. In this project high-risk, high-impact scientific questions will be solved using structure elucidation with the AFM employing a novel tool and novel methodologies.
A combined low-temperature scanning tunneling microscope/atomic force microscope (LT-STM/AFM) with high throughput and in situ electrospray deposition method will be developed. Chemical resolution will be achieved by novel measurement techniques, in particular the usage of different and novel tip functionalizations and combination with Kelvin probe force microscopy. Elements will be identified using substructure recognition provided by a database that will be erected and by refined theory and simulations.
The developed tools and techniques will be applied to molecules of increasing fragility, complexity, size, and three-dimensionality. In particular samples that are challenging to characterize with conventional methods will be studied. Complex molecular mixtures will be investigated molecule-by-molecule taking advantage of the single-molecule sensitivity. The absolute stereochemistry of molecules will be determined, resolving molecules with multiple stereocenters. The operation of single molecular machines as nanocars and molecular gears will be investigated. Reactive intermediates generated with atomic manipulation will be characterized and their on-surface reactivity will be studied by AFM.

Molecular structure elucidation is of great importance in synthetic chemistry, pharmacy, life sciences, energy and environmental sciences, and technology applications. To date structure elucidation by atomic force microscopy (AFM) has been demonstrated for a few, small and mainly planar molecules. In this project high-risk, high-impact scientific questions will be solved using structure elucidation with the AFM employing a novel tool and novel methodologies.
A combined low-temperature scanning tunneling microscope/atomic force microscope (LT-STM/AFM) with high throughput and in situ electrospray deposition method will be developed. Chemical resolution will be achieved by novel measurement techniques, in particular the usage of different and novel tip functionalizations and combination with Kelvin probe force microscopy. Elements will be identified using substructure recognition provided by a database that will be erected and by refined theory and simulations.
The developed tools and techniques will be applied to molecules of increasing fragility, complexity, size, and three-dimensionality. In particular samples that are challenging to characterize with conventional methods will be studied. Complex molecular mixtures will be investigated molecule-by-molecule taking advantage of the single-molecule sensitivity. The absolute stereochemistry of molecules will be determined, resolving molecules with multiple stereocenters. The operation of single molecular machines as nanocars and molecular gears will be investigated. Reactive intermediates generated with atomic manipulation will be characterized and their on-surface reactivity will be studied by AFM.

Max ERC Funding

2 000 000 €

Duration

Start date: 2016-06-01, End date: 2021-05-31

Project acronymARTIVISM

ProjectArt and Activism : Creativity and Performance as Subversive Forms of Political Expression in Super-Diverse Cities

Researcher (PI)Monika Salzbrunn

Host Institution (HI)UNIVERSITE DE LAUSANNE

Call DetailsConsolidator Grant (CoG), SH5, ERC-2015-CoG

SummaryARTIVISM aims at exploring new artistic forms of political expression under difficult, precarious and/or oppressive conditions. It asks how social actors create belonging and multiple forms of resistance when they use art in activism or activism in art. What kind of alliances do these two forms of social practices generate in super-diverse places, in times of crisis and in precarious situations? Thus, ARTIVISM seeks to understand how social actors engage artistically in order to bring about social, economic and political change. Going beyond former research in urban and migration studies, and beyond the anthropology of art, ARTIVISM focuses on a broad range of artistic tools, styles and means of expression, namely festive events and parades, cartoons and comics and street art. By articulating performance studies, street anthropology and the sociology of celebration with migration and diversity studies, the project challenges former concepts, which took stable social groups for granted and reified them with ethnic lenses. The applied methodology considerably renews the field by bringing together event-, actor- and condition-centred approaches and a multi-sensory framework. Besides its multidisciplinary design, the ground-breaking nature of ARTIVISM lies in the application of the core concepts of performativity and liminality, as well as in an examination of the way to advance and refine these concepts and to create new analytical tools to respond to recent social phenomena. We have developed and tested innovative methods that respond to a postmodern type of fluid and temporary social action: audio-visual ethnography, urban event ethnography, street ethnography, field-crossing, and sensory ethnography (apprenticeship). Therefore, ARTIVISM develops new methods and theories in order to introduce a multi-faceted trans-disciplinary approach to the study of an emerging field of social transformations that is of challenging significance to the social sciences.

ARTIVISM aims at exploring new artistic forms of political expression under difficult, precarious and/or oppressive conditions. It asks how social actors create belonging and multiple forms of resistance when they use art in activism or activism in art. What kind of alliances do these two forms of social practices generate in super-diverse places, in times of crisis and in precarious situations? Thus, ARTIVISM seeks to understand how social actors engage artistically in order to bring about social, economic and political change. Going beyond former research in urban and migration studies, and beyond the anthropology of art, ARTIVISM focuses on a broad range of artistic tools, styles and means of expression, namely festive events and parades, cartoons and comics and street art. By articulating performance studies, street anthropology and the sociology of celebration with migration and diversity studies, the project challenges former concepts, which took stable social groups for granted and reified them with ethnic lenses. The applied methodology considerably renews the field by bringing together event-, actor- and condition-centred approaches and a multi-sensory framework. Besides its multidisciplinary design, the ground-breaking nature of ARTIVISM lies in the application of the core concepts of performativity and liminality, as well as in an examination of the way to advance and refine these concepts and to create new analytical tools to respond to recent social phenomena. We have developed and tested innovative methods that respond to a postmodern type of fluid and temporary social action: audio-visual ethnography, urban event ethnography, street ethnography, field-crossing, and sensory ethnography (apprenticeship). Therefore, ARTIVISM develops new methods and theories in order to introduce a multi-faceted trans-disciplinary approach to the study of an emerging field of social transformations that is of challenging significance to the social sciences.

Max ERC Funding

1 999 287 €

Duration

Start date: 2016-09-01, End date: 2022-02-28

Project acronymBactInd

ProjectBacterial cooperation at the individual cell level

Researcher (PI)Rolf Kümmerli

Host Institution (HI)UNIVERSITAT ZURICH

Call DetailsConsolidator Grant (CoG), LS8, ERC-2015-CoG

SummaryAll levels of life entail cooperation and conflict. Genes cooperate to build up a functional genome, which can yet be undermined by selfish genetic elements. Humans and animals cooperate to build up societies, which can yet be subverted by cheats. There is a long-standing interest among biologists to comprehend the tug-of-war between cooperation and conflict. Recently, research on bacteria was successful in identifying key factors that can tip the balance in favour or against cooperation. Bacteria cooperate through the formation of protective biofilms, cell-to-cell communication, and the secretion of shareable public goods. However, the advantage of bacteria being fast replicating units, easily cultivatable in high numbers, is also their disadvantage: they are small and imperceptible, such that measures of cooperation typically rely on averaged responses across millions of cells. Thus, we still know very little about bacterial cooperation at the biological relevant scale: the individual cell level. Here, I present research using the secretion of public goods in the opportunistic human pathogen Pseudomonas aeruginosa, to tackle this issue. I will explore new dimensions of bacterial cooperation by asking whether bacteria engage in collective-decision making to find optimal group-level solutions; whether bacteria show division of labour to split up work efficiently; and whether bacteria can distinguish between trustworthy and cheating partners. The proposed research will make two significant contributions. First, it will reveal whether bacteria engage in complex forms of cooperation (collective decision-making, division of labour, partner recognition), which have traditionally been associated with higher organisms. Second, it will provide insights into the evolutionary stability of cooperation – key knowledge for designing therapies that interfere with virulence-inducing public goods in infections, and the design of stable public-good based remediation processes.

All levels of life entail cooperation and conflict. Genes cooperate to build up a functional genome, which can yet be undermined by selfish genetic elements. Humans and animals cooperate to build up societies, which can yet be subverted by cheats. There is a long-standing interest among biologists to comprehend the tug-of-war between cooperation and conflict. Recently, research on bacteria was successful in identifying key factors that can tip the balance in favour or against cooperation. Bacteria cooperate through the formation of protective biofilms, cell-to-cell communication, and the secretion of shareable public goods. However, the advantage of bacteria being fast replicating units, easily cultivatable in high numbers, is also their disadvantage: they are small and imperceptible, such that measures of cooperation typically rely on averaged responses across millions of cells. Thus, we still know very little about bacterial cooperation at the biological relevant scale: the individual cell level. Here, I present research using the secretion of public goods in the opportunistic human pathogen Pseudomonas aeruginosa, to tackle this issue. I will explore new dimensions of bacterial cooperation by asking whether bacteria engage in collective-decision making to find optimal group-level solutions; whether bacteria show division of labour to split up work efficiently; and whether bacteria can distinguish between trustworthy and cheating partners. The proposed research will make two significant contributions. First, it will reveal whether bacteria engage in complex forms of cooperation (collective decision-making, division of labour, partner recognition), which have traditionally been associated with higher organisms. Second, it will provide insights into the evolutionary stability of cooperation – key knowledge for designing therapies that interfere with virulence-inducing public goods in infections, and the design of stable public-good based remediation processes.

Max ERC Funding

1 994 981 €

Duration

Start date: 2016-09-01, End date: 2021-08-31

Project acronymCELLFUSION

ProjectMolecular dissection of the mechanisms of cell-cell fusion in the fission yeast

Researcher (PI)Sophie Geneviève Elisabeth Martin Benton

Host Institution (HI)UNIVERSITE DE LAUSANNE

Call DetailsConsolidator Grant (CoG), LS3, ERC-2015-CoG

SummaryCell fusion is critical for fertilization and development, for instance underlying muscle or bone formation. Cell fusion may also play important roles in regeneration and cancer. A conceptual understanding is emerging that cell fusion requires cell-cell communication, polarization of the cells towards each other, and assembly of a fusion machinery, in which an actin-based structure promotes membrane juxtaposition and fusogenic factors drive membrane fusion. However, in no single system have the molecular nature of all these parts been described, and thus the molecular basis of cell fusion remains poorly understood.
This proposal aims to depict the complete fusion process in a single organism, using the simple yeast model Schizosaccharomyces pombe, which has a long track record of discoveries in fundamental cellular processes. These haploid cells, which fuse to generate a diploid zygote, use highly conserved mechanisms of cell-cell communication (through pheromones and GPCR signaling), cell polarization (centred around the small GTPase Cdc42) and fusion. Indeed, we recently showed that these cells assemble an actin-based fusion structure, dubbed the actin fusion focus. Our five aims probe the molecular nature of, and the links between, signaling, polarization and the fusion machinery from initiation to termination of the process. These are:
1: To define the roles and feedback regulation of Cdc42 during cell fusion
2: To understand the molecular mechanisms of actin fusion focus formation
3: To identify the fusogen(s) promoting membrane fusion
4: To probe the GPCR signal for fusion initiation
5: To define the mechanism of fusion termination
By combining genetic, optogenetic, biochemical, live-imaging, synthetic and modeling approaches, this project will bring a molecular and conceptual understanding of cell fusion. This work will have far-ranging relevance for cell polarization, cytoskeletal organization, cell signalling and communication, and cell fate regulation.

Cell fusion is critical for fertilization and development, for instance underlying muscle or bone formation. Cell fusion may also play important roles in regeneration and cancer. A conceptual understanding is emerging that cell fusion requires cell-cell communication, polarization of the cells towards each other, and assembly of a fusion machinery, in which an actin-based structure promotes membrane juxtaposition and fusogenic factors drive membrane fusion. However, in no single system have the molecular nature of all these parts been described, and thus the molecular basis of cell fusion remains poorly understood.
This proposal aims to depict the complete fusion process in a single organism, using the simple yeast model Schizosaccharomyces pombe, which has a long track record of discoveries in fundamental cellular processes. These haploid cells, which fuse to generate a diploid zygote, use highly conserved mechanisms of cell-cell communication (through pheromones and GPCR signaling), cell polarization (centred around the small GTPase Cdc42) and fusion. Indeed, we recently showed that these cells assemble an actin-based fusion structure, dubbed the actin fusion focus. Our five aims probe the molecular nature of, and the links between, signaling, polarization and the fusion machinery from initiation to termination of the process. These are:
1: To define the roles and feedback regulation of Cdc42 during cell fusion
2: To understand the molecular mechanisms of actin fusion focus formation
3: To identify the fusogen(s) promoting membrane fusion
4: To probe the GPCR signal for fusion initiation
5: To define the mechanism of fusion termination
By combining genetic, optogenetic, biochemical, live-imaging, synthetic and modeling approaches, this project will bring a molecular and conceptual understanding of cell fusion. This work will have far-ranging relevance for cell polarization, cytoskeletal organization, cell signalling and communication, and cell fate regulation.

Max ERC Funding

1 999 956 €

Duration

Start date: 2016-10-01, End date: 2021-09-30

Project acronymCentrioleBirthDeath

ProjectMechanism of centriole inheritance and maintenance

Researcher (PI)Monica BETTENCOURT CARVALHO DIAS

Host Institution (HI)FUNDACAO CALOUSTE GULBENKIAN

Call DetailsConsolidator Grant (CoG), LS3, ERC-2015-CoG

SummaryCentrioles assemble centrosomes and cilia/flagella, critical structures for cell division, polarity, motility and signalling, which are often deregulated in human disease. Centriole inheritance, in particular the preservation of their copy number and position in the cell is critical in many eukaryotes. I propose to investigate, in an integrative and quantitative way, how centrioles are formed in the right numbers at the right time and place, and how they are maintained to ensure their function and inheritance. We first ask how centrioles guide their own assembly position and centriole copy number. Our recent work highlighted several properties of the system, including positive and negative feedbacks and spatial cues. We explore critical hypotheses through a combination of biochemistry, quantitative live cell microscopy and computational modelling. We then ask how the centrosome and the cell cycle are both coordinated. We recently identified the triggering event in centriole biogenesis and how its regulation is akin to cell cycle control of DNA replication and centromere assembly. We will explore new hypotheses to understand how assembly time is coupled to the cell cycle. Lastly, we ask how centriole maintenance is regulated. By studying centriole disappearance in the female germline we uncovered that centrioles need to be actively maintained by their surrounding matrix. We propose to investigate how that matrix provides stability to the centrioles, whether this is differently regulated in different cell types and the possible consequences of its misregulation for the organism (infertility and ciliopathy-like symptoms). We will take advantage of several experimental systems (in silico, ex-vivo, flies and human cells), tailoring the assay to the question and allowing for comparisons across experimental systems to provide a deeper understanding of the process and its regulation.

Centrioles assemble centrosomes and cilia/flagella, critical structures for cell division, polarity, motility and signalling, which are often deregulated in human disease. Centriole inheritance, in particular the preservation of their copy number and position in the cell is critical in many eukaryotes. I propose to investigate, in an integrative and quantitative way, how centrioles are formed in the right numbers at the right time and place, and how they are maintained to ensure their function and inheritance. We first ask how centrioles guide their own assembly position and centriole copy number. Our recent work highlighted several properties of the system, including positive and negative feedbacks and spatial cues. We explore critical hypotheses through a combination of biochemistry, quantitative live cell microscopy and computational modelling. We then ask how the centrosome and the cell cycle are both coordinated. We recently identified the triggering event in centriole biogenesis and how its regulation is akin to cell cycle control of DNA replication and centromere assembly. We will explore new hypotheses to understand how assembly time is coupled to the cell cycle. Lastly, we ask how centriole maintenance is regulated. By studying centriole disappearance in the female germline we uncovered that centrioles need to be actively maintained by their surrounding matrix. We propose to investigate how that matrix provides stability to the centrioles, whether this is differently regulated in different cell types and the possible consequences of its misregulation for the organism (infertility and ciliopathy-like symptoms). We will take advantage of several experimental systems (in silico, ex-vivo, flies and human cells), tailoring the assay to the question and allowing for comparisons across experimental systems to provide a deeper understanding of the process and its regulation.

Max ERC Funding

2 000 000 €

Duration

Start date: 2017-01-01, End date: 2021-12-31

Project acronymCGCglasmaQGP

ProjectThe nonlinear high energy regime of Quantum Chromodynamics

Researcher (PI)Tuomas Veli Valtteri Lappi

Host Institution (HI)JYVASKYLAN YLIOPISTO

Call DetailsConsolidator Grant (CoG), PE2, ERC-2015-CoG

Summary"This proposal concentrates on Quantum Chromodynamics (QCD) in its least well understood "final frontier": the high energy limit. The aim is to treat the formation of quark gluon plasma in relativistic nuclear collisions together with other high energy processes in a consistent QCD framework. This project is topical now in order to fully understand the results from the maturing LHC heavy ion program. The high energy regime is characterized by a high density of gluons, whose nonlinear interactions are beyond the reach of simple perturbative calculations. High energy particles also propagate nearly on the light cone, unaccessible to Euclidean lattice calculations. The nonlinear interactions at high density lead to the phenomenon of gluon saturation. The emergence of the "saturation scale", a semihard typical transverse momentum, enables a weak coupling expansion around a nonperturbatively large color field. This project aims to make progress both in collider phenomenology and in more conceptual aspects of nonabelian gauge field dynamics at high energy density:
1. Significant advances towards higher order accuracy will be made in cross section calculations for processes where a dilute probe collides with the strong color field of a high energy nucleus.
2. The quantum fluctuations around the strong color fields in the initial stages of a relativistic heavy ion collision will be analyzed with a new numerical method based on an explicit linearization of the equations of motion, maintaining a well defined weak coupling limit.
3. Initial conditions for fluid dynamical descriptions of the quark gluon plasma phase in heavy ion collisions will be obtained from a constrained QCD calculation.
We propose to achieve these goals with modern analytical and numerical methods, on which the P.I. is a leading expert. This project would represent a leap in the field towards better quantitative first principles understanding of QCD in a new kinematical domain."

"This proposal concentrates on Quantum Chromodynamics (QCD) in its least well understood "final frontier": the high energy limit. The aim is to treat the formation of quark gluon plasma in relativistic nuclear collisions together with other high energy processes in a consistent QCD framework. This project is topical now in order to fully understand the results from the maturing LHC heavy ion program. The high energy regime is characterized by a high density of gluons, whose nonlinear interactions are beyond the reach of simple perturbative calculations. High energy particles also propagate nearly on the light cone, unaccessible to Euclidean lattice calculations. The nonlinear interactions at high density lead to the phenomenon of gluon saturation. The emergence of the "saturation scale", a semihard typical transverse momentum, enables a weak coupling expansion around a nonperturbatively large color field. This project aims to make progress both in collider phenomenology and in more conceptual aspects of nonabelian gauge field dynamics at high energy density:
1. Significant advances towards higher order accuracy will be made in cross section calculations for processes where a dilute probe collides with the strong color field of a high energy nucleus.
2. The quantum fluctuations around the strong color fields in the initial stages of a relativistic heavy ion collision will be analyzed with a new numerical method based on an explicit linearization of the equations of motion, maintaining a well defined weak coupling limit.
3. Initial conditions for fluid dynamical descriptions of the quark gluon plasma phase in heavy ion collisions will be obtained from a constrained QCD calculation.
We propose to achieve these goals with modern analytical and numerical methods, on which the P.I. is a leading expert. This project would represent a leap in the field towards better quantitative first principles understanding of QCD in a new kinematical domain."

SummaryThe goal of this project is to explore the fundamental processes which trigger the nucleation and growth of solids. Condensed matter is formed by clustering of atoms, ions or molecules. This initial step is key for the onset of crystallization, condensation and precipitate formation. Yet, despite of the scientific and technological significance of these phenomena, on an atomistic level we merely have expectations on how atoms should behave rather than experimental evidence about how the growth of solid matter is initiated. The classical nucleation theory is commonly in agreement with experiments, provided the original and the final stages are inspected qualitatively. However, the classical theory does not define what fundamentally constitutes a pre-nucleation state or how a nucleus is formed at all. CLUSTER aims at investigating the very early stages of crystalline matter formation on an unprecedented length scale. It shall explore the atomic mechanisms which prompt the formation of solids. Complemented by density functional theory calculations and molecular dynamics simulations, in-situ high-resolution electron microscopy shall be used to investigate the formation, dynamics, stability and evolution of tiniest atomic clusters which represent the embryos of solid matter. Firstly, we investigate the 3D structure of clusters deposited on suspended graphene. Secondly, we focus on cluster formation, the evolution of sub-critical nuclei and the onset of particle growth by thermal activation. Thirdly, using a novel liquid-cell approach in the transmission electron microscope, we control and monitor in-situ cluster formation and precipitation in supersaturated solutions. The results of CLUSTER, which will advance the understanding of the birth of solid matter, are important for the controlled synthesis of (nano-)materials, for cluster science and catalysis and for the development of novel materials.

The goal of this project is to explore the fundamental processes which trigger the nucleation and growth of solids. Condensed matter is formed by clustering of atoms, ions or molecules. This initial step is key for the onset of crystallization, condensation and precipitate formation. Yet, despite of the scientific and technological significance of these phenomena, on an atomistic level we merely have expectations on how atoms should behave rather than experimental evidence about how the growth of solid matter is initiated. The classical nucleation theory is commonly in agreement with experiments, provided the original and the final stages are inspected qualitatively. However, the classical theory does not define what fundamentally constitutes a pre-nucleation state or how a nucleus is formed at all. CLUSTER aims at investigating the very early stages of crystalline matter formation on an unprecedented length scale. It shall explore the atomic mechanisms which prompt the formation of solids. Complemented by density functional theory calculations and molecular dynamics simulations, in-situ high-resolution electron microscopy shall be used to investigate the formation, dynamics, stability and evolution of tiniest atomic clusters which represent the embryos of solid matter. Firstly, we investigate the 3D structure of clusters deposited on suspended graphene. Secondly, we focus on cluster formation, the evolution of sub-critical nuclei and the onset of particle growth by thermal activation. Thirdly, using a novel liquid-cell approach in the transmission electron microscope, we control and monitor in-situ cluster formation and precipitation in supersaturated solutions. The results of CLUSTER, which will advance the understanding of the birth of solid matter, are important for the controlled synthesis of (nano-)materials, for cluster science and catalysis and for the development of novel materials.

SummaryDuring the human lifetime 10000 trillion cell divisions take place to ensure tissue homeostasis and several vital functions in the organism. Mitosis is the process that ensures that dividing cells preserve the chromosome number of their progenitors, while deviation from this, a condition known as aneuploidy, represents the most common feature in human cancers. Here we will test two original concepts with strong implications for chromosome segregation fidelity. The first concept is based on the “tubulin code” hypothesis, which predicts that molecular motors “read” tubulin post-translational modifications on spindle microtubules. Our proof-of-concept experiments demonstrate that tubulin detyrosination works as a navigation system that guides chromosomes towards the cell equator. Thus, in addition to regulating the motors required for chromosome motion, the cell might regulate the tracks in which they move on. We will combine proteomic, super-resolution and live-cell microscopy, with in vitro reconstitutions, to perform a comprehensive survey of the tubulin code and the respective implications for motors involved in chromosome motion, mitotic spindle assembly and correction of kinetochore-microtubule attachments. The second concept is centered on the recently uncovered chromosome separation checkpoint mediated by a midzone-associated Aurora B gradient, which delays nuclear envelope reformation in response to incompletely separated chromosomes. We aim to identify Aurora B targets involved in the spatiotemporal regulation of the anaphase-telophase transition. We will establish powerful live-cell microscopy assays and a novel mammalian model system to dissect how this checkpoint allows the detection and correction of lagging/long chromosomes and DNA bridges that would otherwise contribute to genomic instability. Overall, this work will establish a paradigm shift in our understanding of how spatial information is conveyed to faithfully segregate chromosomes during mitosis.

During the human lifetime 10000 trillion cell divisions take place to ensure tissue homeostasis and several vital functions in the organism. Mitosis is the process that ensures that dividing cells preserve the chromosome number of their progenitors, while deviation from this, a condition known as aneuploidy, represents the most common feature in human cancers. Here we will test two original concepts with strong implications for chromosome segregation fidelity. The first concept is based on the “tubulin code” hypothesis, which predicts that molecular motors “read” tubulin post-translational modifications on spindle microtubules. Our proof-of-concept experiments demonstrate that tubulin detyrosination works as a navigation system that guides chromosomes towards the cell equator. Thus, in addition to regulating the motors required for chromosome motion, the cell might regulate the tracks in which they move on. We will combine proteomic, super-resolution and live-cell microscopy, with in vitro reconstitutions, to perform a comprehensive survey of the tubulin code and the respective implications for motors involved in chromosome motion, mitotic spindle assembly and correction of kinetochore-microtubule attachments. The second concept is centered on the recently uncovered chromosome separation checkpoint mediated by a midzone-associated Aurora B gradient, which delays nuclear envelope reformation in response to incompletely separated chromosomes. We aim to identify Aurora B targets involved in the spatiotemporal regulation of the anaphase-telophase transition. We will establish powerful live-cell microscopy assays and a novel mammalian model system to dissect how this checkpoint allows the detection and correction of lagging/long chromosomes and DNA bridges that would otherwise contribute to genomic instability. Overall, this work will establish a paradigm shift in our understanding of how spatial information is conveyed to faithfully segregate chromosomes during mitosis.

Max ERC Funding

2 323 468 €

Duration

Start date: 2016-07-01, End date: 2021-06-30

Project acronymCorPain

ProjectDissection of a cortical microcircuit for the processing of pain affect

Researcher (PI)Thomas Nevian

Host Institution (HI)UNIVERSITAET BERN

Call DetailsConsolidator Grant (CoG), LS5, ERC-2015-CoG

SummaryIt is a fundamental but still elusive question how nociceptive processing is performed in neuronal networks in the cortex for the conscious experience of pain.
The objective of this project is to identify and characterize the cortical microcircuits in the anterior cingulate cortex (ACC) that are involved in pain processing with cellular resolution. The ACC is essential for evaluating the emotional/affective component of pain. Our research will investigate the elusive question if a dedicated pain circuit exists in the ACC. We will dissect the detailed structure and connectivity of this pain circuit and investigate how it generates affective behavioural responses related to pain.
At the core of this project, we will characterize the neuronal networks in the ACC that are engaged in the processing of noxious stimuli. It will be highly interesting to determine the neuronal dynamics in the ACC during nociception and in chronic pain conditions on the cellular and network level. Furthermore, we will elucidate the downstream targets that are influenced by the pain circuits in the ACC to generate the appropriate behavioural responses.
These aims will be achieved by a combination of electrophysiology, 2-photon Ca2+ imaging and pharmaco- and opto-genetic approaches both in vivo and in vitro and behavioural testing of pain affect in mice.
This project will give a comprehensive picture of how a cortical microcircuit processes afferent noxious stimuli to generate an affective behavioural response. This study will give important insight into the fundamental question of cortical information processing and it is highly relevant to understand pain processing and the changes in the network dynamics that manifest the transition to chronic pain. Eventually this might contribute to the development of novel treatment strategies for this pathological condition.

It is a fundamental but still elusive question how nociceptive processing is performed in neuronal networks in the cortex for the conscious experience of pain.
The objective of this project is to identify and characterize the cortical microcircuits in the anterior cingulate cortex (ACC) that are involved in pain processing with cellular resolution. The ACC is essential for evaluating the emotional/affective component of pain. Our research will investigate the elusive question if a dedicated pain circuit exists in the ACC. We will dissect the detailed structure and connectivity of this pain circuit and investigate how it generates affective behavioural responses related to pain.
At the core of this project, we will characterize the neuronal networks in the ACC that are engaged in the processing of noxious stimuli. It will be highly interesting to determine the neuronal dynamics in the ACC during nociception and in chronic pain conditions on the cellular and network level. Furthermore, we will elucidate the downstream targets that are influenced by the pain circuits in the ACC to generate the appropriate behavioural responses.
These aims will be achieved by a combination of electrophysiology, 2-photon Ca2+ imaging and pharmaco- and opto-genetic approaches both in vivo and in vitro and behavioural testing of pain affect in mice.
This project will give a comprehensive picture of how a cortical microcircuit processes afferent noxious stimuli to generate an affective behavioural response. This study will give important insight into the fundamental question of cortical information processing and it is highly relevant to understand pain processing and the changes in the network dynamics that manifest the transition to chronic pain. Eventually this might contribute to the development of novel treatment strategies for this pathological condition.